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Objectives: To estimate the efficacy of vitamin D supplementation to reduce urgency urinary incontinence (UUI) episodes., Design: Pilot, two-arm, randomized trial conducted from 2013 to 2017. Interventions were 12 weeks of weekly oral 50,000 IU vitamin D3 or placebo., Setting: Academic, university-based outpatient clinic., Participants: Community-dwelling postmenopausal women, 50 years or older, with at least three UUI episodes on 7-day bladder diary and serum vitamin 25-hydroxyvitamin D (25[OH]D) of 30 ng/mL or less., Measurements: The primary efficacy estimate was the percentage change in UUI episodes. Secondary estimates included changes in other lower urinary tract symptoms, along with exploratory subgroup analysis by race/ethnicity and obesity., Results: We randomized 56 women (aged 50-84 years; mean = 60.5 ± 8.2 years), 28 to vitamin D and 28 to placebo; 51 completed treatments. Mean serum 25(OH)D at baseline (21.2 ± 5.2 and 18.2 ± 5.6, P = .30) improved to 57.9 ± 16.3 ng/mL with vitamin D3 and 21.9 ± 8.2 ng/mL with placebo (P < .001). UUI episodes per 24-hour day decreased by 43.0% with vitamin D3 compared to 27.6% with placebo (P = .22). Among black women (n = 33), UUI episodes decreased by 63.2% with vitamin D3 compared to 22.9% with placebo (P = .03). Among obese women, UUI episodes decreased by 54.1% with vitamin D compared to 32.7% with placebo (P = .29). For all women, changes in voiding frequency (P = .40), nocturia (P = .40), urgency (P = .90), incontinence severity (P = .81), and overactive bladder symptom severity (P = .47) were not different between arms., Conclusions: Postmenopausal women with UUI and vitamin D insufficiency demonstrated a greater than 40% decrease in UUI episodes, which did not reach statistical significance compared to placebo, except in the subset of black women. The results of this pilot study support further investigation of vitamin D3 alone or in combination with other treatments for UUI, particularly for women in higher-risk subgroups. J Am Geriatr Soc 67:570-575, 2019., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To investigate the prevalence of urgency urinary incontinence (UUI) at age 68 years and the contribution of vascular risk factors to male and female UUI pathogenesis in addition to the associations with raised body mass index (BMI)., Subjects and Methods: In all, 1 762 participants from the Medical Research Council (MRC) National Survey for Health and Development birth cohort who answered the International Consultation on Incontinence Questionnaire short form (ICIQ-SF), at age 68 years, were included. Logistic regression was used to estimate associations between UUI and earlier life vascular risk factors including: lipid status, diabetes, hypertension, BMI, previous stroke or transient ischaemic attack (TIA) diagnosis; adjusting for smoking status, physical activity, co-presentation of stress UI symptoms, educational attainment; and in women only, type of menopause, age at period cessation, and use of hormone replacement therapy (HRT)., Results: UUI was reported by 12% of men and 19% of women at age 68 years. Female sex, previous stroke or TIA diagnosis, increased BMI and hypertension (in men only) at age 60-64 years were independent risk factors for UUI. Female sex, increased BMI, and a previous diagnosis of stroke/TIA increased the relative risk of more severe UUI symptoms. Type and timing of menopause and HRT use did not alter the estimated associations between UUI and vascular risk factors in women., Conclusion: Multifactorial mechanisms lead to UUI and vascular risk factors may contribute to the pathogenesis of bladder overactivity in addition to higher BMI. Severe UUI appears to be a distinct presentation with more specific contributory mechanisms than milder UUI., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Subjects and Methods: • Secondary analysis of anonymous data from 10,434 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan was performed. Data were prospectively collected through the central register from men diagnosed with LUTS in 1100 medical institutions between October 2004 and March 2005. • Those who had received an α1-adrenoceptor antagonist within 1 week before the initial visit were excluded. • The survey items were International Prostate Symptom Score (IPSS), quality of life (QOL) score, and patient characteristics including age, bodyweight, body mass index, and LUTS-related comorbid conditions. • Data on IPSS items were used in a hierarchical cluster analysis (Ward's method)., Results: • Of 10,434 men with LUTS, 9910 were included in the analysis after 5% data trimming (524 patients). Five symptom clusters were identified and the symptom types of each cluster were examined. • The largest cluster (27%) consisted of patients with multiple severe symptoms, i.e. complaining of six or more symptoms with a mean score ≥2.8. In contrast, the second smallest cluster (13%) consisted of patients with minimal symptoms, i.e. complaining of essentially one or two symptom with a mean score ≤2.1. • The other three clusters were labelled based on their dominant symptoms. The clusters were weak stream (27%), storage symptoms (21%) and voiding symptoms (12%). • The storage symptoms group was older, and had more comorbidities. • The distribution of the QOL score was different among the clusters, and the percentage of patients who were very dissatisfied was highest in the multiple severe symptoms group and lowest in the minimal symptoms group., Conclusions: • Cluster analysis using the IPSS showed that men with LUTS can be classified into five characteristic symptom groups. • A new approach to symptom-based classification may be useful to elucidate the pathology of male LUTS and individualize the therapeutic strategy for affected patients, but further studies are needed., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes., Materials and Methods: • In this 12-week, double-blind, double-dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12., Results: • A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05). • Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively., Conclusions: • In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To assess the measurement characteristics of the Patient Perception of Intensity of Urgency Scale (PPIUS) in patients with overactive bladder (OAB)., Patients and Methods: • Adult women with at least a 3-month history of OAB. The design was a 4-week, double-blind, randomized, placebo-controlled trial of transdermal oxybutynin, with a 2-week placebo run-in and 8-week, open-label extension. • Symptom improvement was assessed using 3-day bladder diaries incorporating the PPIUS, and disease-specific health-related quality of life was assessed using the King's Health Questionnaire (KHQ). Convergent validity was shown by correlation with the KHQ, and other bladder diary variables. Known groups validity was assessed by comparison of baseline mean urge ratings, and urgency episode frequency for continent and incontinent patients, and by comparison with the same measures from a historical control group of 40 asymptomatic female volunteers. • Between- and within-groups responsiveness was assessed using standardized effect sizes (Cohen's d and effect size r). Reliability was assessed for the two arms of the trial at different time points and intervals, using intraclass correlation (ICC) and a t-test for the difference between mean scores., Results: • In total, 96 women were randomized. Urgency episode frequency showed moderate correlation with total KHQ score (r = 0.500, P < 0.001) and with daytime and night-time voiding frequency. • There were significant differences in continent and incontinent subgroups for mean urge ratings (difference in means, -0.61/void, P < 0.001), and urgency episodes (difference in means, -2.67 episodes/day, P < 0.001), as well as between OAB patients and normal controls (mean urge rating: difference in means 1.22 per void, P < 0.001; urgency episodes: difference in means 2.93 episodes/day, P < 0.001). • Between-groups analysis of effect size found that urgency episode frequency (d = 0.679, r = 0.321) was more responsive than mean urge rating (d = 0.480, r = 0.233). In both subgroups, urgency episode frequency (d = 0.421-0.454, r = 0.206-0.222) had better within-groups responsiveness than mean urge rating. • Urgency episodes (ICC, 0.65-0.81) were measured more reliably than urgency urinary incontinence episodes (ICC, 0.50-0.65)., Conclusions: • Assessment of urgency episodes using the PPIUS shows good reliability, excellent known groups validity, high responsiveness and convergence with subjective measures of severity. • PPIUS is freely available, and should be useful in both clinical practice and research studies when assessing women with urgency, with or without urgency urinary incontinence., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To assess patient selected goal improvement with transdermal oxybutynin, in a representative population of adult women with overactive bladder (OAB)., Subjects and Methods: Adult women with ≥ 3 month history of OAB symptoms, with or without urgency urinary incontinence, were recruited from a tertiary referral urogynaecology unit. Participants were allocated to either transdermal oxybutynin 3.9 mg/day or matching placebo patches in a double-blind, randomized parallel group design, over 4 weeks. Patient-selected goal achievement was defined as the primary outcome measure. Participants selected their own goals for treatment at baseline, and subsequently scored achievement of these goals on a visual analogue scale. They completed 3-day bladder diaries incorporating the Patients Perception of Intensity of Urgency Scale (PPIUS) to assess urgency and urgency incontinence episodes. Quality of life was assessed using the King's Health Questionnaire (KHQ)., Results: A total of 96 women were randomized; 78 (81.3%) participants completed 4 weeks double-blind treatment. There was no significant difference between mean goal achievement in the transdermal oxybutynin and placebo groups (41.9% (SD 31.3) vs 32.2% (SD 27.3), P= 0.203). Transdermal oxybutynin was associated with significant improvements in urgency episodes (-1.23 episodes/day (SD1.40) vs -0.21 episodes/day (SD 1.58), P= 0.01). Both groups made non-significantly different improvements in KHQ scores; 18 (38.2%) patients in the transdermal oxybutynin group experienced either erythema or pruritus, with 7 (14.9%) experiencing at least one systemic adverse event., Conclusions: In women with OAB, in comparison with placebo, transdermal oxybutynin 3.9 mg/day leads to significant objective improvements in urinary urgency, but with no significant difference observed in achievement of patients' own goals for therapy, or improvement in disease specific quality of life., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To describe our initial outcome data following a shortened 6-week treatment protocol with percutaneous tibial nerve stimulation (PTNS) in women with overactive bladder syndrome (OABS) unresponsive to bladder retraining and anticholinergic therapy., Patients and Methods: This was a prospective observational study over a 6-month period. In all, 43 women with OABS refractory to medical therapy were treated with a shortened PTNS protocol that consisted of 6 weekly 30 min sessions. Bladder symptom diaries and health-related quality of life (HRQL) assessed using the short-form seven-item self-report. Incontinence Impact Questionnaire (IIQ-7) were completed before and after treatment. A positive response was defined as: (i) OAB symptoms no longer being bothersome; (ii) reduction by half in frequency episodes and (iii) reduction by 25% in IIQ-7 outcomes., Results: All 43 women (median age 55.3 years) completed six treatments with a positive response rate of 69.7%. In the positive responders, the median daytime and nocturnal frequency was reduced by half after 6 weeks of treatment (11.8 vs 6.9 and 3.5 vs 1.8, respectively, P < 0.05) and the patients reported fewer urge leak episodes per 24 h (median 3.5 vs 2.4, P < 0.05). The median IIQ-7 scores improved by 25% (30.4 vs 24.3, P < 0.05) in responders, while the median number of pads changed in 24 h also decreased by 34% (3.8 vs 2.5, P < 0.05). The median acceptability of the technique when scored by Visual Analogue Score was 9.6/10 and no side-effects were reported., Conclusion: A shortened 6-week treatment with PTNS appears to be successful, with a significant reduction in symptoms and improvement in HRQL. This early data suggest that the duration of treatment for peripheral neuromodulation can be halved compared with the conventional 12 weeks, which would make it more acceptable and cost effective for patients. A randomised controlled trial of 6 weeks vs 12 weeks of PTNS therapy would be useful in determining the optimal duration of treatment., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: to investigate the effect of menopausal transition and age on symptoms of urinary incontinence in midlife., Subjects and Methods: the study included a nationally representative cohort of 1211 women followed up since their birth in 1946 and annually from 48-54 years; their menopausal transition status and symptoms of stress, urge, and severe urinary incontinence (UI) at 7 consecutive years from ages 48-54 were assessed., Results: from Generalized Estimating Equations, women who became perimenopausal ('pre-peri') or those experiencing perimenopause for >1 year ('peri-peri') were more likely to have symptoms of stress UI than were postmenopausal women; the odds ratio (95% confidence interval) was; pre-peri 1.39 (1.11-1.73); and peri-peri 1.39 (1.4-1.71). Menopausal transition status was not associated with urge or severe UI. These relationships were not explained by age, childhood enuresis, reproductive factors, previous health status, body mass index and educational qualifications., Conclusion: this study is unique in being able to disentangle the effects of age, menopausal transitions, and other life-long risk factors on UI. Menopausal transition was only related to stress UI, while increasing age was related to both stress and urge UI. This study suggests that there are both shared and distinct aetiological pathways leading to each type of UI.

Objectives: To determine whether baseline urgency urinary incontinence (UUI) episodes predict the need for increased doses of fesoterodine in patients with overactive bladder (OAB), as clinicians would benefit from data that help to predict which patients require higher doses of antimuscarinics to manage UUI episodes., Patients and Methods: In this pooled analysis of data from two double-blind, placebo-controlled trials, patients were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks and stratified into tertiles (>0-<2, 2-<4, or > or =4) according to the number of UUI episodes/24 h as recorded in 3-day bladder diaries at baseline. The change in mean UUI episodes/24 h from baseline to end of study was assessed using analysis of covariance., Results: In a post hoc analysis of data from two clinical trials, there were significant reductions from baseline in UUI episodes for fesoterodine 4 and 8 mg vs placebo in patients (n) with >0-<2 (422), 2-<4 (424) and > or =4 (481) UUI episodes at baseline (all P < 0.01). In patients with 2-<4 and > or =4 UUI episodes at baseline, fesoterodine 8 mg gave significantly greater mean reductions (-1.92 and -4.17, respectively) vs fesoterodine 4 mg (-1.43 and -3.31) (P < 0.05). The most common adverse events were dry mouth (placebo, 8%; fesoterodine 4 mg, 19%; and 8 mg, 35%) and constipation (placebo, 2%; fesoterodine 4 mg, 5%; and 8 mg, 6%)., Conclusion: Fesoterodine 4 and 8 mg significantly reduced UUI episodes vs placebo; this effect appeared to be greater with fesoterodine 8 mg in patients with > or =2 UUI episodes/24 h at baseline. Fesoterodine was well tolerated, although higher doses increased the incidence of adverse events. These findings might aid the clinical identification of patients with OAB who would most benefit from increasing the dose of fesoterodine from 4 to 8 mg.

Objective: To compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder., Patients and Methods: Medical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination., Results: At 16 study centres, 621 children aged 5-14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2-0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%)., Conclusion: Propiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3-4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin.

Objective: To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB)., Patients and Methods: In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8 voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period., Results: Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively., Conclusion: In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated.

Objective: To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model., Patients and Methods: In all, 306 women (aged 21-84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for > or =3 months. Participants were also required to have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR)., Results: Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention., Conclusion: In this trial, duloxetine was better than placebo for treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL.